Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD: A Pilot Randomized Cross-Over Study

Abstract

Background and objectives: We examined the effect of alkali replacement for metabolic acidosis on vascular endothelial function in patients with CKD.

Methods: We performed a pilot, prospective, open-label 14-week crossover study examining the effect of oral sodium bicarbonate treatment on vascular function in 20 patients with an eGFR of 15-44 ml/min per 1.73 m² with low serum bicarbonate levels (16-21 mEq/L). Each period was 6 weeks in duration with a 2-week washout period in between. Patients were treated to goal serum bicarbonate of ≥23 mEq/L. The primary end point was change in brachial artery flow-mediated dilation (FMD) between treatment and control conditions. Secondary end points included changes in markers of inflammation, bone turnover, mineral metabolism, and calcification.

Results: Eighteen patients completed the study and were included in the primary efficacy analysis. The mean (SD) age and eGFR were 59 (12) years and 26 (8) ml/min per 1.73 m², respectively. Serum bicarbonate increased significantly with sodium bicarbonate treatment (+2.7±2.9 mEq/L, P≤0.001), whereas there was no change in bicarbonate levels in the control group. FMD significantly improved after sodium bicarbonate therapy (mean±SD, FMD baseline: 4.1%±4.1%; 6 weeks: 5.2%±2.9%; P=0.04) There was no significant change in FMD in the control group (mean±SD, FMD baseline: 4.6%±3.1%; 6 weeks: 4.1%±3.4%; P=0.20). Compared with control, sodium bicarbonate treatment resulted in a significant increase in FMD (mean, 1.8%; 95% confidence interval, 0.3 to 3.3; P=0.02). There was no significant change in bone markers or serum calcification propensity with treatment. Serum phosphorus and intact fibroblast growth factor 23 increased significantly during treatment.

Conclusions: Treatment of metabolic acidosis with sodium bicarbonate significantly improved vascular endothelial function in patients with stages 3b and 4 CKD.

Keywords: Alkalies; Bicarbonates; Bone Remodeling; Brachial Artery; Calcification, Physiologic; Control Groups; Cross-Over Studies; Dilatation; Fibroblast Growth Factors; Goals; Inflammation; Minerals; Phosphorus; Phosphorus, Dietary; Pilot Projects; Prospective Studies; Renal Insufficiency, Chronic; Sodium Bicarbonate; acidosis; chronic kidney disease; chronic metabolic acidosis; fibroblast growth factor 23; glomerular filtration rate; vascular disease.

Graphical abstract

Figure 1.

Study design.

Figure 2.

Percent flow-mediated dilation at baseline and 6 weeks after sodium bicarbonate administration or control. FMD, flow-mediated dilation.